The phase 3 melanoma (MEL) study CheckMate 067 showed improved progression-free survival and objective response rates with N + I or N versus ipilimumab monotherapy, with treatment-related grade 3/4 adverse events (AEs) reported in 55%, 16%, and 27% of patients (pts), respectively. The objective of this analysis was to assess the safety profile associated with reduced infusion times for N + I (from 180 to 90 min) and N (from 60 to 30 min) using data from a phase 1 biomarker study (CA209-038).
The primary objective of the study was to assess the pharmacodynamic activity of N + I and N on the tumor microenvironment. Exploratory objectives included assessment of safety, tolerability, and pharmacokinetics of reduced infusion times for N + I and N. Pts with previously treated or untreated MEL were divided into 4 non-randomized groups with different follow-up times: N + I (1 mg/kg + 3 mg/kg Q3W for 4 doses then N 3 mg/kg Q2W for either 180 min [N + I 180 group, n = 27] or 90 min [N + I 90 group, n = 36]) or N (3 mg/kg Q2W for either 60 min [N 60 group, n = 85] or 30 min [N 30 group, n = 20]). Pts were treated for up to 2 years or until confirmed disease progression or intolerable toxicity.
Across the 4 study groups (n = 168), the majority of pts did not experience an infusion (97%) or hypersensitivity (96%) reaction. 5 (3%) pts had any grade infusion reaction and 3 (2%) experienced any grade hypersensitivity; no grade 3/4 infusion or hypersensitivity reactions were reported. In the N + I 180 and N + I 90 groups, 4% and 8% of pts, respectively, had 1 or more infusion interruptions; in the N 60 and N 30 groups, the rate was 14% and 5%, respectively. The rate of treatment-related grade 3/4 AEs for N + I 180, N + I 90, N 60, and N 30 groups was 52%, 31%, 5%, and 0%, respectively.
Reducing the infusion times for N + I (from 180 to 90 min) and N (from 60 to 30 min) resulted in similar low levels of infusion reactions, suggesting that this approach may speed up treatment administration for pts and treatment centers. Additional data on safety, pharmacokinetics and response rates will be presented.
Clinical trial identification
Legal entity responsible for the study
S. Martin-Algarra: Advisor and speaker in boards and educational events organized by BMS J.B. Haanen: Served as a consultant for MSD, Roche, and Pfizer, and received research funding from BMS & GSK. C. Horak: Employed by and owns stock in BMS. S. Bhatia: Institution has received research funding from BMS. A. Ribas: Owns stock in Kite Pharma and consultant for Pfizer, Roche, Amgen. C.L. Slingluff, Jr: Honoraria from Castle Biosciences and holds a patent with UVA Licensing and Ventures Group, research funding from GSK, Merck, BMS, Polynoma, and 3M, and his institution has served in an advisory role for Polynoma and Immatics Biotechnologies. W.H. Sharfman: Served as a consultant for Merck and received research funding from BMS. M. Callahan: Received research funding from MSKCC and has a family member employed at BMS. F.S. Hodi: Served as a consultant for BMS, received research funding from BMS, and has a patent pending for an immune target. J.D. Wolchok: Honoraria: EMD Serono and Janssen Oncology; consultant: BMS Merck, MedImmune, Ziopharm, Polynoma, Polaris, Jounce, GSK; research funding: BMS, MedImmune, GSK and Merck; co-investor in a patent for DNA vaccines of cancer in animals; travel funding: BMS. J. Luke: Institution received research funding from BMS. T.C. Young, A. Qureshi: Employed by BMS. W.J. Urba: Consultant for Celldex, Green peptide, MedImmune, BMS. All other authors have declared no conflicts of interest.